Rare Diseases Aren’t That Rare, But Stem Cells Could Help Make Them So

Rare diseases are anything but rare – with more than 7,000 uniquely identified, they cumulatively affect more than 300 million patients worldwide. The majority of these diseases affect children, and only 5% have FDA-approved treatments. Therapeutic development is often hindered by the lack of disease models that allow scientists to identify potential treatments.

Stem cells open up a new world of possibilities for studying and treating rare diseases, and thanks to technologies such as the NYSCF Global Stem Cell Array®, our automated platform for creating stem cells from patient skin or blood, researchers everywhere can more easily jumpstart studies into these devastating conditions.

What makes rare diseases so hard to study and treat?

Many rare diseases are the result of a single genetic mutation that causes dysfunction in the body. However, identifying the disease-causing mutation — which has become easier due to genome sequencing technology — doesn’t solve the puzzle.

“One challenge for scientists is that a patient with a rare disease might present with symptoms, but it is unclear what is driving those symptoms,” explained Daniel Paull, PhD, Senior Vice President of Discovery and Platform Development at NYSCF. “We may know that a mutation exists, but scientists still need to understand how that mutation is causing the disease.”

Another hurdle is that researchers need to study the impact of the mutation in multiple individuals to draw meaningful conclusions. For rare diseases that only impact a select number of people, collecting tissue samples and data from enough volunteers can be difficult.

“The challenge then becomes finding enough subjects that share that same alteration to have statistically enough power to do research with,” continued Dr. Paull. “ Having only a limited amount of material can make that a challenge from a pharmaceutical perspective. It is very expensive to make drugs. So, for rare diseases, sadly, the challenge is how will you recoup the research and development costs that it would take to get a drug to market?”

How can stem cells help?

One advantage of stem cells is that they can be used to create any cell type in the body, helping researchers tease apart the impact of a mutation.

“Stem cells have the ability to make all the cell types that could be affected by the disease, so we can look for what is going wrong across a number of different tissues to see which ones are changing or behaving differently,” said Dr. Paull. “We can even gene edit stem cells to correct the disease-causing mutation and observe exactly how the cells react, giving us valuable insight into the impact of that mutation.”

Using NYSCF’s unique proprietary automation and artificial intelligence capabilities, scientists can survey these features broadly, potentially identifying new drivers of disease that would have never been studied otherwise.

“We have developed analyses that are ‘disease-agnostic’ – meaning that they can be applied to any cell type for any disease, and they aren’t reliant on looking for a known disease characteristic,” explained Dr. Paull. “Instead, we can measure several different cellular features and how they differ in patient cells versus healthy cells.”

And because stem cells can generate any cell type, they can be used to create biobanks of cells and disease models that can be easily replicated and distributed to labs around the world.

“We are making our standardized models of rare diseases available to the community, so when a researcher wants to expand their collection, or if they’re looking for a rare disease that might tie into another more common disease, we can provide them with cells,” noted Dr. Paull. “So, for rare-disease-focused foundations that want to encourage researchers to actually do research into a given disease, instead of having to go through the expense of patient recruitment and stem cell generation, we’ve already made these repositories available.”

Which rare diseases does NYSCF study?

“We’ve worked with rare diseases basically since the birth of the Array in 2011,” remarked Dr. Paull. “Samples from the National Institutes of Health (NIH) undiagnosed disease program were among the first cells that we used our technology on.”

Some of the rare diseases NYSCF has studied include Charcot-Marie-Tooth disease, Batten disease, Hereditary Hemorrhagic Telangiectasia (HHT), NGLY1 deficiency (in collaboration with Grace Science Foundation), and infantile neuroaxonal dystrophy (INAD).

“For example, with INAD, which we work on in collaboration with a foundation called INADcure, we are making stem cells from INAD-affected families and gene editing these cells to correct the disease-causing mutation and pinpoint exactly how it drives dysfunction, hopefully accelerating treatment development,” said Dr. Paull. 

In many cases, studying rare diseases can also offer insights into more common diseases.

“INAD shows many similarities to Parkinson’s, and other rare diseases likely share mechanisms with more common diseases as well,” explained Dr. Paull. “It could be that a therapeutic strategy found to be beneficial for a rare disease holds value for many other diseases. And more broadly, rare diseases further our understanding of basic human biology, which can be applied to all disease research.”

What’s next for NYSCF’s rare disease research?

Our immediate focus at NYSCF is to leverage our technology to find new therapies for rare diseases. By screening FDA-approved drugs on patient cells, scientists can find new leads for slowing or reversing the drivers of a disease.

“We are also interested in exploring how we can use our platform to identify already-approved therapeutics that can be repurposed to potentially treat diseases for which there is no other treatment or cure available,” said Dr. Paull.

With an unlimited supply of patient cells made from stem cells, scientists can test a wide variety of therapeutics ‘in the dish,’ including newly developed approaches.

“Everyone’s very excited about mRNA right now for the COVID-19 vaccine, but there’s also potential for mRNA-based therapies to be very beneficial for rare diseases,” noted Dr. Paull. “And our platform and stem cell models allow us to test these different hypotheses, which is very exciting for the prospect of finding new therapies.”

To hear more about the unique challenges faced by rare disease patients and how stem cell research is advancing treatments and cures, watch a recent panel discussion here: