The UB participates in a consortium to develop a new drug for the treatment of Huntington’s disease

Huntington’s disease is a neurological disease caused by a mutation in the huntingtin gene (HTT) that leads to motor, cognitive, and psychiatric disorders. It is a serious condition that affects around one in 10,000 people and, so far, there is no cure or effective treatment to slow its progression. Researchers at the University of Barcelona (UB) are taking part in a consortium working on the research and development of a new drug to treat the cognitive and motor decline associated with the disease. The initiative is led by the company Medibiofarma and involves the collaboration of the Hospital Sant Pau Research Institute (IRHSP).

“The project will significantly contribute to advancing the clinical development of a new treatment for Huntington’s disease, an area of human healthcare with a high need for effective solutions. In addition, the data generated will further our knowledge of important signalling pathways related to proteins called histone deacetylases (HDACs), which appear altered in this and other neurodegenerative diseases,” explains Esther Pérez-Navarro, a professor at the Faculty of Medicine and Health Sciences of the UB, principal investigator of the Kinases and Phosphatases in Neuronal Function and Dysfunction Research Group and one of the coordinators of the project, together with Dr. Verónica Brito, leader of the Molecular Biology of Huntington’s Disease Group at the UB.

A drug that improves synaptic connections

The drugs currently available for the treatment of Huntington’s disease are aimed at treating its symptoms, especially chorea, the involuntary movements associated with the disorder. “An effective treatment for this and other neurodegenerative diseases would be one that is capable of altering neurodegeneration, that is, one that is able to completely halt neuronal death or significantly delay it, so that the course of the disease slows down and clinical symptoms are alleviated permanently or for long periods of time,” explain these two UB researchers, who have more than 20 years’ experience in researching the molecular and biochemical aspects of Huntington’s disease.

The drug MBF-015, developed and patented by Medibiofarma, is a histone deacetylase inhibitor. HDACs are enzymes that remove acetyl groups from histones, leading to increased DNA compaction and decreased gene expression. The inhibitor MBF-015 is a small molecule capable of crossing the blood-brain barrier, gaining access to the brain and blocking two distinct forms of these proteins: HDAC1 and HDAC2. This selective impact avoids the adverse effects of inhibiting all variants of HDAC1 and HDAC2.

In addition, the compound has shown robust efficacy in preclinical studies in control animals and in animal models of neurodegeneration, in which an improvement in synaptic connections and the formation of new connections have been observed.

Advancing clinical development of the product

The consortium’s main objective is to advance the clinical development of MBF-015, which has already entered a Phase I clinical study in healthy volunteers. At this stage, researchers will continue with the evaluation of the most appropriate dose and start a Phase IIa study to analyse the safety and tolerability of the drug. “The idea is to take the development of the product to the start of a multicentre Phase IIb clinical trial with a larger number of patients to explore the efficacy of the treatment,” concludes Esther Pérez-Navarro.

The project, with reference number SCPP2200C009575, has obtained 240,820 euros in funding, which has been awarded to the UB within the framework of the 2022 call for public-private collaboration projects of the 2021-2023 Spanish National Plan for Scientific, Technical and Innovation Research, as part of the Recovery, Transformation and Resilience Plan.