- Date: February 28, 2021
If you are diagnosed with a rare disease, it’s likely that your doctor will have never treated or even heard of your condition before. In fact, you may be the only person in your town—or even your country—who suffers from it. This is the reality for the more than 300 million people across the globe who have a rare disease, defined as a disease that affects less than 1 in 2000 people. There are an estimated 7000 conditions that meet this criteria.
Patients and families not only feel isolated, but in many cases it can take several years to even receive the correct diagnosis. While onset can occur any time from birth to late adulthood, about 50% of those affected are children and 95% of rare diseases currently have no approved treatment.
To change this scenario and secure a treatment for each patient as well as delay the progression of each rare disease, “la Caixa” Foundation supports the development of innovative therapies through the CaixaImpulse acceleration program. To date, 11 such projects, addressing an array of rare diseases ranging from muscular disorders to childhood cancers and more, have received financial aid as well as training and mentoring.
Today, on the international Rare Disease Day, we spoke to the leaders of three CaixaImpulse projects that tackle rare diseases: Valle Palomo, a scientist at the Center for Biological Research (CIB-CSIC), University of Valencia researcher Beatriz Llamusi and Albert Quintana from the Autonomous University of Barcelona (UAB).
Innovative target for ALS
"Rare diseases disturb the entire lives of the people who suffer from them, and usually in a very incapacitating manner. These people deserve to have therapeutic options.
"ALS is a devastating illness that causes the progressive loss of the motor neurons that control muscles. Most patients die within 2 to 4 years of receiving a diagnosis. Thanks to the Ice Bucket Challenge, ALS research funds have increased considerably and we are now starting to see the results. In particular, novel therapeutic targets are being discovered that will help us tackle the disease from different angles.
"One such target is TDP43, a molecule that doesn’t work properly in ALS patients -- and has recently also been found to malfunction in Alzheimer's disease, which goes to show that research into rare diseases also benefits those who suffer from more common conditions.
"The aim of our project is to develop a drug that restores TDP43 and thus reverses neuromuscular degeneration. Our agent has had promising results in preclinical trials, and thanks to the support of CaixaImpulse it is now licensed and currently undergoing the regulatory studies to obtain approval to perform clinical trials in humans."
A world-first drug for myotonic dystrophy
Beatriz Llamusi leads the CaixaImpulse project ”Therapeutic modulation of MBNL1-2 gene expression in myotonic dystrophy”, which is now a spin-off of the University of Valencia called Arthex Biotech S.L., of which Llamusi is CEO and Co-founder.
"All diseases deserve our attention, even if they are not highly prevalent. In the case of myotonic dystrophy, the condition that we are developing a treatment for, there are over 1 million people who suffer the severe and debilitating effects of this disease, in addition to the huge burden of having to see many different specialists.
"While there have been many advances in understanding the mechanisms of myotonic dystrophy in recent decades, there’s still no effective therapy. Just one drug has made it to the phase I clinical trial, but not beyond.
"The drug that we are developing will boost the production of muscleblind-like (MBNL) proteins in patients’ muscular cells. It is a lack of these proteins that causes the severe muscle weakness and wasting seen in myotonic dystrophy. Ours is the first and only project that targets microRNAs as a therapeutic strategy against this disease. CaixaImpulse allowed us to create a valorisation plan to see if it was feasible to bring it to market. We have now selected one candidate molecule, and we hope to start clinical trials in human patients early next year."
CBD to treat mitochondrial diseases
Albert Quintana leads the CaixaImpulse project MitoCBD, a CBD-based treatment for a severe type of mitochondrial disease known as Leigh syndrome.
"For many years, research into rare diseases wasn’t seen as profitable, and so they were often neglected. Thankfully, this has been changing in recent years. The attitude now is that, even if just 1 in every 5000 children is affected, as is the case with mitochondrial diseases, we owe it to these kids to try to figure out what’s going on, and work out how we can give them a better life.
"Leigh syndrome affects about 1 in 40,000 live births and leaves patients severely disabled. Children are generally diagnosed within the first few months of life, and most do not survive to see their tenth birthday.
"The major symptoms are caused by neuronal death, often due to high oxidative stress. We tested CBD, an antioxidant and neuroprotective compound, in mouse models of Leigh syndrome and we got really promising results; both a reduction in symptoms and an increase in lifespan.
"CaixaImpulse has helped our project progress through the preclinical stages, and we are going to start clinical trials in human patients early next year. Since CBD—a safe and well-tolerated drug—is already approved, we can fast-track its development, and we expect it to reach the market within the next five years. We believe that CBD could also be a solution for other diseases, particularly those where there is a similar mechanism of neuronal death."
Since 2015, the CaixaImpulse programme has also brought eight other innovative projects that address rare diseases closer to the clinic. These include a deep learning technology to optimize the treatment of Dravet syndrome led by Sandra Acosta from UPF, and three gene editing technologies; Uni-large, led by Marc Güell from UPF, ROUTER, led by Puri Fortes at CIMA, Universidad de Navarra, and FRATAXAV, led by Antoni Matilla from IGTP.
Two projects are developing treatments for multiple sclerosis; ITH13001 which is led by Rafael León Martínez at Hospital Universitario de la Princesa, and Specialised pro-resolving lipid mediator, led by Rubèn López Vales from UAB. Finally, Robert Soliva at Barcelona Supercomputing Centre leads PELE-e, a software for the optimization of enzymes, and Meritxell Teixidó leads the IRB Barcelona project Gate2Brain.
This article also appears on the Blog CaixaCiencia.
More programme highlights
January 20, 2021
We recently interviewed Gate2Brain CEO Meritxell Teixidó to learn more about this innovative technology.
November 10, 2020
In a recent interview, CaixaImpulse project leader Marc Güell tells us some of the secrets behind his project Uni-large.
October 19, 2020
In honour of World Breast Cancer, we interviewed some of the researchers who are working with the support of the "la Caixa" Foundation to combat this disease.