Ask HN: How to raise funds for rare disease research?
My beautiful daughter Nil (3yo), has a rare genetic disorder called Kleefstra Syndrome (KS). She cannot walk or talk at this point. Doctors believe she will walk eventually, but speech they are not so sure about. KS involves partial chromosome deletion (or sometimes mutation) of a particular gene, EHMT1, which in turn causes a protein called GLP not to be produced. Moderate to severe Intellectual disability, limited/absent speech are some of the symptoms.
KS was first “discovered” in 2010. Thanks to “whole genome sequencing”, it is now possible to diagnose KS with a single draw of blood. Maybe that’s why we are hearing about KS kids more often in our community.
We have a non-profit foundation based in the US ( https://www.idefine.org ) to improve awareness and lead/fund potential research for KS. Also, there are already two active pieces of research that provide potential improvement for these kids. One explores drug repurposing ( https://www.nature.com/articles/s41467-019-12947-3 ), the other is about supplementing the missing proteins ( https://www.sciencedaily.com/releases/2021/09/210921100245.h... ). Both have very promising results but are not close to clinical trials yet.
Still, several potential treatment modalities need to be explored in depth. Antisense Oligonucleotide Therapy (ASO), gene therapy (CRISPR), drug repurposing are a few modalities to name.
Known KS individuals sum up to only a few hundred patients so far. When the patient count is so low, pharmaceutical companies are not interested in pursuing research for that disease, so patient organizations are forced to fund their research themselves. This has been done by several rare disease patient organizations before. Batten Disease (Beyond Batten Disease Foundation funded $35M research), Angelman Syndrome (Fast Foundation funded $26M research), SMA (Cure SMA funded $35M research), all funded successful research and managed to reach clinical trial level.
Sorry about the extra-long intro, but I wanted to provide context for this relatively “new” genetic disease which is hardly known. Since HN has members with extensive digital marketing experience, I’m hoping you would share your ideas with us. Long story short, if we can manage to raise several million to kickstart multiple types of research in parallel, then we can offer these kids a chance.
My first idea is about co-hosting a series of Instagram live streams with celebrities to ask for donations for research. I’m not sure if this is already a solid fundraising technique? Also, I don’t know the first thing about finding celebrities as well.
A second idea is, recording a youtube video and promoting it using google ads grants.
At this point, we want to leave no stone unturned about fundraising.
So here we are. Any advice would be greatly appreciated.
211 comments
[ 4.7 ms ] story [ 224 ms ] threadHere’s a good post, he’s a prolific blogger: https://matt.might.net/articles/rare-disease-internet-matchm...
(Edit: this is a bigger picture post detailing the whole process: https://matt.might.net/articles/my-sons-killer/)
Depending on the kind of research you are looking to get funding for, you might also look into an NIH SBIR grant or something. https://rarediseases.info.nih.gov/tips/pages/124/
Also, I've put much of what I've learned online:
https://bertrand.might.net/articles/algorithm-for-precision-...
It is a deeply frustrating position to be in, wanting to work on these rare diseases and help this rarified patient population and not being able to, even though me and my colleagues are poised to do so. I often get maligned for being a scientist in pharma; laypeople often assert that I "don't want to treat cancer / rare genetic disease / etc; because then I'd be out of business." I can assure those reading that all of us DESPERATELY would like to work in these indications, and often times it's tragically finance that dictates whether we are able to or not. The system feels broken.
Personally, I'm a computational/mathematical biologist and I work on single cell data targeting multiple myeloma, I'd really like to see serious non-profit Pharma. Drug repurposing seems like the most feasible avenue. What I know of right now is open Pharma [2].
[1] https://dtp.cancer.gov/timeline/flash/milestones/M3_CCNSC.ht... [2] https://www.ospfound.org
Are there any possibilities that you see from your experience in using modeling or other in silico methods to reduce time in the lab, find new leads in drug development, or otherwise enhance research capabilities?
As far as in silico, I think absolutely there are probably opportunities here. Generative models might be useful for some type of counterfactual (automated) reasoning with respect to disease course/treatment. I think we're in the relatively early days of collecting high resolution cellular data, so I think in silico approaches like this will be more and more relevant.
[1] https://clue.io
Perhaps the interesting thing would be to ask what particular thing makes the US different to other western countries, rather than cherry picking one particular thing that happens to agree with whatever ideology is popular today.
Obviously this can't work in the current pharma industry configuration; what financial incentive is there for big pharma companies to publish their results for another company to beat them to a new drug? I don't have a solution to this problem, but I hope someday we as a society can find one. This would absolutely revolutionize biopharmaceutical science.
I've thought that a type of cryptographic data commons based on multi-party communication [1] could possibly be deployed with some effect. Basically you need algorithms that can compute on encrypted data, and a way to securely communicate encrypted data. There might not be huge incentive to use something like this, but maybe a version of this idea could work.
[1] https://en.wikipedia.org/wiki/Secure_multi-party_computation
I only have a rudimentary understanding of blockchain technologies, but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.
Another idea would be to completely socialize all biopharmaceutical research, but that type of system would require an extremely radical societal shift.
> but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.
I think ultimately this is how a research cooperative could work. If distributing and re-allocating fractional ownership is efficient enough, it seems like something like this might be feasible. The idea with multiparty communication (MPC) is that in this setup a research entity would contribute their data in an encrypted fashion, and any parties would be granted access to compute on it based on some set of rules/buy in etc.
This is a really difficult technical approach, as MPC is really only in it's infancy, made only to seem easy by the far more difficult and distant prospect of socializing medicine, which would seem to be of the greatest benefit.
I understand that there are no easy choices here, and having to make a choice will always be heartbreaking.
May I suggest contacting MacKenzie Scott (Jeff Bezos' ex) who seems to be looking for worthwhile endeavors to finance.
(I have no connection to Ms Scott, I just read articles about her charitable activities in the newspaper.)
I hope we can get in touch somehow. Thank you.
I think that more people studying rare diseases would result in a net gain of lives saved; I don't think it's as zero-sum as "either 1 person's life is saved or 10 are" in this instance.
Research also cross pollinates across disease areas. For example, understanding altered metabolism in cancer can yield insights for non-oncological metabolic disorders. Oftentimes, though, nobody's working on translating that work out of a cancer model, because the financial incentives are not there.
The 1962 FDA effectiveness mandates have had the side effect of increasing drug development costs enormously, and that shuts down development of treatments for rare disorders.
The Kefauver Harris Amendment you refer to was immensely important towards the development of safe and efficacious drugs -- I do not see the connection between that act and rare disease therapeutic development. In fact, drugs that only offer marginal improvements in quality of life for rare genetic disease patients are often fast-tracked by the FDA. Requiring that a drug _works_ shouldn't inhibit drug development. Otherwise, we end up with tragedies like what happened with the use of thalidomide, which prompted this amendment in the first place.
Sure, competition also creates waste, which is your main point here, but don't discount the upsides.
Competition has proven itself in the real world. Having only one monolithic vaccine maker (whether for-profit, non-profit, or government) would be a very bad thing. What would happen if it falls to corrupt leadership, as one of many examples of how this could go wrong? There is no mechanism to escape badness here, because we only have 1 of them.
Large scale collaborative scientific endavours like CERN show us that it is possible to both publically share knowledge and still explore multiple avenues and competing designs. There's also no financial profit motive and while CERN receives a lot of public funding, it has to pump that funding back into the economies of the funding countries so it serves more like a high-tech industry stimulus and technological incubator.
I see no reason why a similar aproach for the development of (specific) therapeutics could not work.
Much larger cooperative structures are less proven to work and are more hypothetical, though, even if CERN is an example of such a structure working. The risk, mainly, is that there isn't a good corrective mechanism if the whole thing becomes corrupted or rotten from the top. The other risk is that the cooperation is actually detrimental to progress because it correlates outcomes via group think. Some decorrelation is nice. I am happy that Musk et al. weren't forced to become cogs at NASA, and could explore their own ideas, which was easier to achieve by then being explicitly separate entities (even if they were reliant on contracts).
the profit motive in a multinationally funded system is still there in the sense of 'we have a budget of X, what's the best way to spend it?'. And research avenues that fail to yield the expected results can be terminated. In my experience, disagreement between researchers or groups were also far from uncommon. But maybe that's just physicists being exceptionally knowitall^H^H^H hard to convince :)
It's not flawless, but I don't think it could be less efficient use of public money than the current system where we publically fund early research and the succesfull projects get snatched up by the industry, patented, and sold for large profits. Even if a lot of pharmaceutical research ends up going nowhere (or a competitor beats them to it), we still end up paying for it trough the profit margins of the parent companies.
Raising healthcare costs are a serious concern for many countries, and part pharmaceuticals are a non-trivial part of the cost. Researching and producing them locally might help reduce that cost and stimulate a broader healthcare industry.
I do fear that pharmaceutical research might be to politicized for a multinational approach(e.g. HIV, what disease to prioritize). And there's bound to be some backlash from certain groups over a large 'shadowy' multinational body doing human trials.
If we can use a software analogy, mess like Windows 95 wouldn't see the light of the day. But they were useful nonetheless.
[1] “Operation Warp Speed”
there are some examples, for instance enzastaurin being repurposed for vascular EDS, after washing out as an angiogenesis inhibitor for cancer. I don't know if it makes sense mechanistically, I sure hope it does.
Both. We're not even close to our limits on research capacity.
If we actually were at the limits of research capacity, and we were actually forced to make decisions between livesaving treatments to research where we couldn't do both without sacrificing something else that saves lives, then yes, of course, choose the thing with the highest number of predicted lives saved. But we're not even close to needing to make such decisions yet.
We just don't have a good system for funding cures you can't sell to millions. That's not anywhere close to "heartbreaking decisions" territory; that's "societal coordination problem" territory.
Really? From the outside it seems to me like we are beyond our limits on research capacity.
The progress seems to be slowing down everywhere while the price per discovery of a new drug skyrockets with many having rather disappointing efficacy (high NNTs).
Maybe not at your stage of research, but it's my understanding that further down the pipeline (eg clinical trials) you're mich closer to the limits, simply due to financial constraints: given that a trial for something you can sell to millions isn't that mich more expensive than one you can sell to dozens,and given that you need to get payed for your job, i don't see how it doesn't make sense to prioritize the lower hanging fruit. Am i missing something?
(Full disclosure: close family member works at $bigPharma)
I don't think it's about finding treatments you can "sell to millions", it's that in pharma, like in pretty much every other business, it's about ROI.
You definitely don't need millions of patients, but you do need to cover the R&D costs _and_ have enough left over to keep the shareholders happy.
It may well be(!), so let's assume you're right, what better incentive structure should we put in place instead?
Increase general taxation and use that to fund more pharamaceutical R&D?
For many politicians that would be seen as a "courageous decision" (hat-tip: Sir Humphrey Appleby)
> and let them only be at-cost (!) manufacturers
Won't it be hard to find investors if you do that?
> move all R&D off to universities
I think the "D" in "R&D" might be the problem in this approach. Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.
Better that than paying negative interest for German 20 year bonds, if you ask me.
> Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.
Agreed, universities have historically not been involved into the development part. But that is not a given dogma that can't be changed - the government could fund the establishment of development departments.
Alternatively, international governments could establish cooperative efforts to develop pharmaceutical compounds. Rare diseases and the decline of available reserve antibiotics are a global problem affecting every country on Earth just the same.
Development = taking a lot of candidate compounds and evaluating them in the classic three-stage procedure - phase 1: determine how the compound is processed in actual human bodies to check if it is actually safe to ingest and what side effects can already be observed (n ~ 20-80), phase 2: determine effective dosage (n ~ 100-500), phase 3: check effectivity in a double-blind trial (n ~ 1k-10k), as well as the fourth phase (after-license monitoring) [1][2].
The more a compound progresses, the more expensive the trials get to conduct, not just because the participants usually get some compensation for their risk, but also because all the data has to be tracked and processed. And a lot of candidate compounds fail somewhere along the path (either because they are ineffective or because the side effects are too severe), which makes the money invested effectively wasted (from a capitalist point of view, not from a scientific!).
[1]: https://en.wikipedia.org/wiki/Clinical_trial
[2]: https://studienteilnehmergesucht.de/ratgeber/die-vier-phasen...
At least one $bigPharma defines "research" as being everything up to and including the first proof of concept in a human [Phase I] trial. After that would be "development".
My grandmother had rheumatoid arthritis, and it made her life utterly miserable for her last 10 years. Recently, Enbrel was developed by a biotech for profit company, it is the first effective treatment for rheumatoid arthritis.
No university or government came up with it. A for profit company did.
Take the US military budget and give it to life saving research instead of life taking.
Edit: Also implement a wealth tax instead of income tax. Discourage hoarding of wealth and concentration of power in the hands of top 1%.
Not in % of gdp. The only metric that matters. The US economy is massive in size so of course the budget is a big number.
> one of which is china manages to defend itself with a tenth of the budget.
Everything is cheaper in China. You can do a lot more with one million there than in the US.
edit: BTW, is there any actual proof that this whole military budget dissuades Russia and China in any way?
It has produced far, far better results than communist incentive structures.
Maybe twenty years from now some people with a high degree of knowledge, skills, and some resources will be able to get around these hoops illegally (by the laws of certain jurisdictions) and fix these conditions (or kill themselves or somebody else trying, but so does god/nature and doctors, with different[citation needed] probability distributions).
The diseases like what OP is dealing with are the ones that are going to advance science for all of us. That’s where gene therapies are going to be applied first which will pave the path for more mass-market treatments.
When Martin Shkreli bought the rights to Daraprim, some of his rhetoric about pharmaceutical industry sounded fair. He said that he is willing to send the drug for free to anyone who wrote to the company and he was essentially making the insurance companies pay the absurd price of the drug. He claimed no patient would ever financially suffer for the drug. He said the needed the money to pay for new research and better drugs and it was one of of lesser of evil thing he can do to R&D.
Ignoring the trickle down effect, if the government and Insurance companies in most cases ultimately pay for the price of medication wouldn't it be valid motivator to research rare diseases?
Not sure if there's as viable for OP since only a few hundred people have been diagnosed.
Shkreli's ideology was when it comes to innovation in Pharma and America's patent driven capitalist nature towards it is the reason why America leads the way in innovation.
I guess for decisions about pharma research like this having an elected body or representation of an elected body is a good thing.
In the USA the best of the best are put in charge of tomorrows medicine, and that is why they succeed while the rest of the world is just pitiful in comparison.
I'm just extrapolating incentives. Is there any incentive to cure (invoice once), when they can treat (life long invoices)? Certainly scorn is irrelevant as OPs comment suggests they're unwilling to work on rare diseases. And these companies are public. They have shareholders that expect them to constantly grow.
I don't believe it's a stretch to say, at the very least, the incentive is there.
You know many people who would have died of smallpox,measles, polio, and the like 100 years ago, you just have no idea who those people are.
To be clear, I still think this conversation goes on in the background. Bill Gates famously convinced Oxford not to give the covid vaccine IP away thus preventing poorer countries from creating their own vaccines. The deaths from this act alone should be enough to convince you that money makes medicine murkier than you clearly want to believe.
I'm familiar with the idea of re-purposing drugs for rare disease treatments (most of my adjacent work has been in very early-stage academic research), but I'm curious about the financials here. Could some of the financial risk here be minimized by aggregating multiple groups of patients, all suffering from different rare diseases? From what I know about the process, the answer is yes, but I'd be curious to hear from somebody closer to the process.
However, for a player like me, it’s worth me operating in the 500k to 25mil range and buying businesses there because, first off I’m not a millionaire, and second, I can assemble a group of related small businesses which collectively would make 25 million which I can then sell to private equity for a larger multiple than I bought them for.
My point being, is there a way to create some kind of collective of rare disease causes and raise money as a group, collectively funding the labs and salaries of scientists to work on these diseases, ideally in an efficient way so that the work done on one disease can, at least partially, be effective for a number of the diseases in the group.
I don’t know the answer, I just wanted to offer an idea from my perspective.
I'd start with a simple campaign page with your mission, your goals, some cute pics and some way to collect donations and capture emails. There's loads of fundraising CRMs out there. Givelively is a decent one and costs nothing but there's plenty of options. Even just a Facebook page could work.
As for how to acquire leads from scratch that's a tough one. Ads can work, you can also try reaching out to media orgs to try to get some airtime to talk about your campaign.
Your ideas all sound fantastic, and definitely on the right path, maybe reaching out to foundations of other rare syndromes may offer some help, likewise with Facebook groups, and the like. I run my own non-profit https://sterlingstrong.foundation to bring awareness to KS, CHD, isomerism, etc, and to help families during long ICU stays, and further research by donating to other research centers such as https://www.kennedykrieger.org, maybe they, or orgs like Center for Rare and Neglected Diseases https://crnd.nd.edu/directors-page may help? I wish you and your family all the best!
> How to raise funds for rare disease research?
I'm not a marketing expert (though I do work with rare diseases). But a good starting point might be to checkout https://www.rarebeacon.org/ There certainly is help and there are options, but as you understand finding and accessing them isn't always easy. Good luck on your journey
https://chanzuckerberg.com/science/programs-resources/rare-a...
Meta aimed to build a knowledge graph of published research papers.
Patient driven research/rare is one is a separate program focused on supporting patients with rare diseases connect with and support scientists studying those diseases and the larger rare diseases network.
1. AllStripes (https://www.allstripes.com/) -> It might be worth reaching out to them to get put in contact with other foundations that might be working on the same thing.
2. Reaching out to RareBase (https://www.rarebase.org/) or Ethan Perlstein (https://mobile.twitter.com/eperlste) to talk about how they work with similar foundations.
3. There is a new company called (https://www.vibebio.com/) that are working on helping fundraise for patient communities using DAOs. I think Alok Tayi is one of the founders there.
4. I know there are some tech founders with family members of rare disease that have gone through similar experiences. For example, I think Rohan Seth at clubhouse has one (https://www.lydianaccelerator.org/). They might be good resources to reach out too.
our family experienced something similar when a loved one fell ill and therapeutic options were unavailable. feel free to ping me at atayi@vibebio.com - happy to connect and see how we can help.
our vision is to realize every cure for every community. rare diseases is where we are starting.
and thanks Sri for the shout-out!
About twenty years later, he was grown up and was soon to have a family, when the son of a family friend was diagnosed in infancy with the same form of cancer - except it was even more rare. This strain is almost always manifested below the neck (like my uncle), but in this child, it was in his brain. It has been a battle, but the boy was able to fight through it several times. Multiple resurgences later, he is finally recovered: thanks to the research done on my uncle.
All that to say, research on rare diseases is extremely important and something I am very passionate about.
NIH provides funding and accelerator programs for medical startups. If you have the expertise, apply yourself, or find a grant writer to help you fill it out all out. The programs themselves are great and they provide a ton of support. Funding is in steps (e.g. step 1 - $200k, step 2 - $1mil).
I'd also recommend https://wefunder.com/ of who I know many of the folks running it and it is great, but the NIH route is more specific to your case.
I feel your pain about wanting more R&D around treatments and potential cures but finding almost nothing because it wouldn't be commercially viable.
My main strategy was trying to contribute with what I know best: software development. The company I joined (lifebit.ai) is building tooling to reduce medical/pharma R&D costs, in an effort to make it economically viable to research diseases that weren't viable before. This is a mission I can get behind and that feels like the best use of my time.
I hope you get to find the best way to have the biggest impact. Good luck!
Universities have something called an indirect rate. This is basically how they pay for things that a private company would build into the overall cost of the project. Things like administrative folks, and lights, and heat, and IT support for the internet, etc., because "direct costs" are only what applies directly to your project.
These are often 50%+, and tend to come as a shock to people, even when the total cost is well less than private research firms.
The thing that doesn't get talked about as much is if you're a funder, if you have somewhere on your site, the funding announcement, etc. that you're capping indirects at say, 15%, that it's much easier for researchers to convince university administration to use that lower rate (in that if you don't have it, we're SOL).
So if you do ever manage to head that direction, please do make sure to include something like that.
The other kind is about drugs that are out of patent, like Ketamine, which very likely can cure important diseases, but since no one stands to make back the money it costs to get them approved, they remain illegal.
Of course, I'm not at all a billionaire, but some of them read HN.
So, a win-win emerges: PSP patients get well-funded clinical trials of therapies designed to address their affliction and the entire world gets improved understanding of therapies that target Alzheimers.
If there is something special about KS that allows it to be a diagnostic for therapies in adjoining disease with broader impact, then suddenly an avenue opens for intense investment in therapies for KS.
https://news.ycombinator.com/item?id=29287200
It also includes a link to this:
https://www.resetera.com/threads/guy-cures-himself-of-lactos...
As you note with a patient pool of the order of hundreds, they are likely to be very scattered and so if you can get together a cohort for a medical trial, it makes it much easier for Pharmaceutical companies to test repurposed drugs against that cohort.
* I think it was linked to here on HN. Apologies for the shoddy search terms but the only things I can remember about their story was: the parents both dropped out of software jobs to get biochem (or biomed?) PhDs to research the disease (don't remember what) and the ease of cohort accessibility was their number one takeaway for their retrospective blog post(?). If you can find that blog post its well worth a read for all the non-technical (i.e. logistical/financial etc.) aspects of rare disease research.
A good friend of mine founded a startup to try and solve this and I was about to join her full time when the pandemic unfortunately crushed it, especially as they couldn't find a real business model.
It would be quite interesting as a non-profit entity though.
There are tricks to this kind of stuff, and some people know the tricks. I guess the first step is knowing that it's a real skill, that people know how to do it well and you need to learn from them. I suspect they'd be willing to share them given the circumstances.
Now their existing donors may also be helpful, but you seem to be jumping a step.
This is what they specialize in. Feel free to e-mail me if you need help getting the conversation started there, I know a few of their MDs and researchers.
EDIT: Apologies, I see this has already been recommended and Matt has himself replied. Best of luck!