Convegno Annuale LIRH 2021 - locandina

LIRH Annual Conference: Towards the Cure of Huntington Disease - December 3, 2021

Pharmaceutical companies confront researchers and patients on the HD treatments perspectives

The future of therapeutic research to cure Huntington's disease.

This is the title of the LIRH Foundation 2021 Annual Conference, which will take place online next Friday 3 December, from 15.00 to 17.30 CET.

Representatives of the world's leading pharmaceutical companies involved in Huntington's disease trials will meet with the best researchers in the field of rare diseases and with patients: all seated at the same virtual table for a unique opportunity of its kind on the research progress to find effective treatments for Huntington's disease.

The Italian excellence in HD clinical research has been recognized worldwide thanks to the work of Lirh and his scientific Officer, prof. Ferdinando Squitieri, principal investigator of all HD clinical trials carried out in Italy.

During the conference, the developments on pridopidine, a molecule in phase III trial  under the guidance of Prof. Squitieri in our Country, will also be announced. Pridopidine has recently obtained the designation of 'fast track' by the Food and Drug Administration, a recognition that could accelerate and facilitate the time to market as an investigational drug.
Prof. Michael R. Hyden, scientist and CEO of Prilenia, will tell us more.

The conference will take place online on the Rafiky platform and will guarantee simultaneous translation from Italian into English. Dr Barbara D'Alessio, President of Lirh, Dr. Simonetta Massafra, Head of UOC Clinical Research Institute Mendel IRCSS Casa Sollievo della Sofferenza and Health Director of the CSS-Mendel Institute of Rome and Professor Ferdinando Squitieri, head of of the Research Unit on Huntington's Disease of the IRCCS Casa Sollievo della Sofferenza in San Giovanni Rotondo and the Mendel Institute in Rome.

The conference will be attended by representatives of pharmaceutical companies with innovative therapies being tested: Michael A. Panzara, Wave Life Sciences, Daniel Leonard and Sara Ying, uniQure, Beth Borowsky, Novartis and Anu Bhattacharyya, PTC Therapeutics will illustrate the data that emerged from previous studies and the prospects for future trials.

Researchers and patients will also be able to take part in the discussion with questions and insights.

You can download the program HERE

You can learn more about the speakers HERE

In order to participate, please click HERE

Video tutorial in Italian, available HERE


Summary of the clinical studies being presented in the Conference



Phase III study, currently underway also in Italy, randomized, double-blind, placebo-controlled, which intends to evaluate the efficacy and safety of pridopidine in patients with early stage Huntington's disease. Pridopidine binds to and activates the Sigma-1 receptor (S1R), a protein very present in the brain. The S1R receptor regulates key cellular pathways commonly compromised in neurodegeneration. By activating this receptor, pridopidine appears to favor the connections between nerve cells and between important brain structures that are compromised by the disease and to preserve neurons from cell death induced by mutated huntingtin protein (mHTT). The molecule recently received the 'fast track' designation by the FDA. Results are expected in 2023.



Phase IIB clinical study with Branaplam, the first drug capable of reducing huntingtin levels also in peripheral tissues to be administered orally and not intrathecally (with lumbar puncture). Branaplam reduces mRNA and HTT protein expression, as confirmed in a Phase I study. The protocol for a Phase IIb study in early-stage patients has now been finalized, with the aim of identifying a safe dose and well tolerated of branaplam which reduces mRNA sufficiently to achieve clinical benefit. A preliminary part of the study will determine the dose, while part 2 will be an open-label extension of the selected dose. 11 countries are expected to participate, including Italy, and the recruitment of the first patient is scheduled for late 2021/early 2022.



A Phase I study in healthy volunteers is currently underway with PTC518, a small molecule that reduces RNA and, consequently, the HTT protein. Like branaplam, this molecule is also bioavailable orally, is able to penetrate the blood-brain barrier and is expected to act in both the nervous system and peripheral tissues. We are closely following the developments of phase I with the hope that our country can be involved in a later phase of the study.



Phase 1b/2a, multicentre, randomized, global-scale study to investigate investigational drug WVE-003 in adult patients with early Huntington's disease, expressed as SNP3 single nucleotide polymorphism. SNPs are normal variations in DNA, a sort of genetic fingerprint that allows a 'selective' approach to the mutated protein. The presence of SNP3 allows WVE-003 to specifically target the mRNA of the mutated (toxic) huntingtin protein, leaving the healthy huntingtin protein relatively intact. Only those patients who have SNP3 in their DNA can participate in this preliminary study. Italy will participate in this study expected in early 2022 and SNP3 seems to be very well represented in Italian patients.



The Phase I/II CT-AMT-130-01 study is the first FDA-approved clinical trial for gene therapy in Huntington. In addition to safety and tolerability, the duration of persistence of AMT-130 in the brain will be evaluated. This gene therapy is made up of a small piece of synthetic genetic material - called microRNA (miRNA) - that is transported and inserted into cells using a previously modified and rendered harmless adeno-associated virus (AAV) that only infects nerve cells. . Once inside a cell, the miRNA targets the RNA molecule that carries the instructions needed to produce huntingtin and hits it, with the aim of degrading it and reducing its quantity. The study is not selective for mutated huntingtin and requires MRI-guided neurosurgery. Treatment in early stage patients started as early as in the US in June 2020 and the Phase Ib / II (no control group) planned open-label study in the EU and UK.



SOM3355 (bevantolol hydrochloride) works as a beta blocker, inhibiting the vesicular monoamine transporter 2 (VMAT2). Produced by the Spanish company SOM Biotech, it was originally developed to treat hypertension and is marketed in Japan, South Korea and China with this indication. Its potential in Huntington's disease has emerged thanks to an AI-powered drug screening platform - run by SOM Biotech - that is used to identify existing drugs that can be reused for use in new indications. SOM3355 has already passed a Phase 2a study, improving the involuntary and jerky movements known as chorea in the participants. The next study will be an international Phase IIb study to evaluate the efficacy of SOM3355 in reducing chorea in two parallel doses followed by an open label extension. The study will begin in 2022, also in Italy.