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February Monthly Edition 2024

Prof Mart Saarma, GeneCode CSO & Board Member: “Our mission is a simple question we ask ourselves — can we slow down or stop neurodegeneration when treating chronic neurological diseases?”


The development of innovative treatment strategies for neurodegenerative diseases is of utmost priority for numerous reasons. In the context of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS) and Huntington’s, the complexity of their pathophysiology requires sophisticated treatment methods. These diseases are becoming more common as the world’s population ages, which has increased the need for efficient treatments. The treatments that are currently available mostly control symptoms without substantially slowing the course of the disease. Innovative strategies have the potential not only to address symptoms but also to modify the course of these diseases. From an economic perspective, these diseases are expensive to manage, and effective treatments could lead to a significant decrease in long-term healthcare spending.

Globally, various companies are developing novel treatment methods for neurodegenerative diseases, but GeneCode stands out from the rest. GeneCode Ltd., established in 1993 in Tallinn, Estonia, is a multinational R&D company focusing on neurodegenerative diseases. The company specializes in proprietary drug design technologies, creating novel small-molecule drug candidates for diseases like Parkinson’s, Alzheimer’s, ALS, Multiple Sclerosis, and others, aiming for neuroprotective and potentially restorative treatments. GeneCode’s approach is unique because it aims for disease modification and potential cures rather than symptom management. The company’s drug design methods and technologies are globally patented, forming the basis of GeneCode’s innovative technological platforms.

In conversation with Prof Mart Saarma, CSO & Board Member of GeneCode

Q. What was the motivation behind starting GeneCode?

Our main mission is to find conceptually new treatments for neurodegenerative diseases, and our first focus is Parkinson’s disease (PD). In PD, so-called dopamine (DA) neurons degenerate and die, and all current drugs and treatments fail to slow down or stop neurodegeneration. We develop a drug that slows down and stops neurodegeneration and perhaps even restores damaged nerves. About 10 million people are suffering from the disease, and because the population is aging, it is expected to double by 2030. All current treatments alleviate motor symptoms, but our approach should allow for the treatment of non-motor symptoms as well.

Q. Can you explain about your services in brief?

Neurons are postmitotic cells, i.e., they do not divide and are as old as we are. They also need support to stay alive, and in humans, this is provided mainly by proteins called neurotrophic factors. Until now, three major classes of proteins have shown efficacy in animal models: glial cell line-derived neurotrophic factor (GDNF) family members GDNF and neurturin (NRTN), platelet-derived growth factor B (PDGF-B), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF) of the CDNF-MANF family. We discovered GDNF receptors, and CDNF was found and characterized in my lab. GDNF family growth factors bind to cell surface receptors and send a signal to the cells—to stay alive, regenerate axons, and enhance the activity of the dopaminergic system. GDNF protein has shown efficacy in activating DA neurons in the last phase II clinical trial, and post hoc analysis showed in almost 50% of the patients that GDNF had clear therapeutic effects.

GDNF protein, however, has limitations: it does not penetrate through the blood-brain barrier (BBB) and needs brain surgery. Because surgery is invasive and risky, treatment can only be started on later-stage patients, often with less than 20% of their DA neurons left. GDNF diffuses poorly so that it does not reach all sick neurons in the brain and does not have effects on non-motor symptoms such as constipation, motivation, sleep disorders, depression, pain, etc.

Q. GeneCode’s mission focuses on slowing down or stopping neurodegeneration. How does this mission drive your day-to-day operations and long-term strategy?

We first developed the BT13 compound and demonstrated Proof of Concept; it binds specifically to GDNF receptors GFRa1-RET and protects DA neurons, but it was not good enough for the clinic. We wanted to improve the efficacy, solubility, BBB penetration, and stability of the compounds, and then, with French and UK partners, we optimized the compounds. The current best compound is almost 1000 times more effective than BT13, passes via the BBB, and efficiently protects and rescues mouse and human DA neurons. In vitro data indicate that they can potentially treat non-motor symptoms. The advantages of our new compounds compared to GDNF or other neurotrophic factor proteins or gene therapy are:

  1. Systemic delivery is used, and no brain surgery is needed; therefore, treatment can be started shortly after PD diagnosis when many DA neurons are still alive.
  2. Diffuses well in tissues and can help neurons to survive and regenerate.
  3. Can treat both motor and non-motor symptoms.
  4. A small molecule is cheap to produce and has broader use.
  5. It can be used to treat several other diseases: amyotrophic lateral sclerosis, retinitis pigmentosa (RP), constipation, Hirschsprung disease, inflammatory bowel disease (IBD), obesity, etc.

Q. What are the biggest challenges GeneCode faces in drug discovery and development, and what opportunities do you foresee in the biotech industry?

Compared with competitors, GeneCode offers a novel, breakthrough solution that, once on the market, may help patients by slowing progression and potentially reversing disease. The treatment can be used in early-stage PD patients soon after diagnosis. It is important to stress that we can also treat non-motor symptoms that significantly affect patients’ quality of life. Later stages carry higher costs and a lower quality of life than earlier health states. Preventing progression to worse health states may have a profound and significant cost benefit to the health system by reducing the cost associated with disability and long-term care.

Q. How do you market your services?

Our best marketing strategy is to showcase our results. Last year, we received a grant and equity investment option from the European Innovation Council Accelerator program for 16 million euros. For the second 2023 EIC Accelerator cut-off in March, 551 businesses submitted a full application. A set of 51 companies from 17 different countries were selected in a highly competitive process to receive the funding. In addition, we highlight our achievements by filing patents and presenting our research in top-tier publications and conferences.

Q. Do you have any new services ready to be launched?

We started IND-enabling studies for Parkinson´s disease this year and hope to begin with clinical Phase I at the end of next year. In addition to PD, we are also focusing on other indications such as ALS, IBD, and RP.

Q. What does the future hold for your company and its customers? Are exciting things on the way?

GDNF Mimetics is a platform technology. Based on our first-generation compound BT13 optimization, we created more than 1100 new compounds. Around 10 compounds show characteristics suitable for new drug candidates. We are starting proof-of-concept studies in three different new indications: ALS, RP, and IBD.

Prof Mart Saarma, SCO & Board Member

“GENECODE scientific partners have published more than 600 publications with more than 40, 000 citations and are inventors or coinventors of more than 50 patent families and patents.”