Experimental ALS Treatment Shows Promising Results in Phase 1 Clinical Trials

Motor neuron diseases, also called motor neuron diseases, are rare neurodegenerative pathologies that progress to progressive paralysis. To date, no treatment has demonstrated lasting effectiveness. However, researchers have recently developed a drug candidate that could significantly curb the disease. It has shown encouraging results in phase 1 trials.

Motor neurons are nerve cells located in the brain and spinal cord. They are divided into two subcategories: upper and lower motor neurons, responsible for transmitting signals from the brain to the muscles in order to orchestrate movements. In motor neuron diseases (MMN), these cells deteriorate, interrupting signal transmission and causing, in many cases, progressive paralysis.

MMNs come in two main categories. Higher forms primarily affect neurons in the motor cortex, usually manifesting with symptoms such as stiffness and some clumsiness. Conversely, lower forms affect cells located in the ventral horn of the spinal cord, notably causing muscle weakness, cramps, involuntary contractions and wasting. When they reach the motor nuclei of the cranial nerves, these pathologies result in progressive facial paralysis and swallowing disorders.

Among these diseases, amyotrophic lateral sclerosis (ALS), commonly known as Charcot disease, is the most common. In France, there are 2.7 new cases per 100,000 inhabitants per year. Although its causes remain largely unknown, approximately 15% of cases are hereditary, often linked to a mutation in the superoxide dismutase gene. ALS is characterized in particular by cramps, motor problems, speech difficulties and muscle contractions. In approximately 10% of cases, it is associated with frontotemporal dementia (FTD), leading to behavioral problems.

Since the late 1990s, riluzole has remained the best-known treatment for slowing the progression of ALS. Other drugs, such as edaravone, sodium phenylbutyrate and Qalsody (based on tofersen), have been added to the therapeutic arsenal. However, their benefits, although modest, remain uncertain in the long term. Faced with these limitations, researchers at the University of Queensland (UQ) took on the challenge of designing an effective and sustainable candidate therapy.

A Hope Named NUN-004

After more than twenty years of research into MMN, Professor Perry Bartlett of the Queensland Brain Institute (QBI) and Professor Andrew Boyd have developed a drug aimed at slowing the progression of the disease and improving patients’ motor skills. Called NUN-004, this treatment targets ALS, which represents approximately 90% of MMNs. “ There are currently only three drugs approved worldwide to slow the progression of ALS and partially improve quality of life. None, however, can reverse the disease “, Professor Bartlett said in a statement. It highlights the urgent need to develop new treatments.

To evaluate the effectiveness of NUN-004, a phase 1 trial was conducted on a cohort of 28 participants, including 8 ALS patients and 20 healthy subjects. The latter received single doses of NUN-004 administered intravenously, increasing gradually, while the patients received multiple doses over a six-month period. The researchers analyzed four main endpoints: safety, single- and multiple-dose pharmacokinetics, and targeted antibodies against the drug.

Promising results

According to the results, published in the journal Clinical Drug
InvestigationsNUN-004 was well tolerated by all participants, with no reported adverse effects or antibody responses. “ ALS patients showed signs of disease stabilization and, notably, reported anecdotal improvements in gross and fine motor skills. “, clarified Professor Bartlett.

The development of this drug is based on the understanding of a key protein, EphA4, involved in guiding motor neurons towards the spinal cord. This protein, according to researchers, hinders the healing process of motor neurons after injury. By blocking its action, the team hopes to preserve motor functions and slow the progression of the disease. “
We are extremely encouraged by the results of this study “, confided Professor Bartlett.

With the success of this first phase, the team now hopes to obtain the necessary funding to continue its work. “ This research could also pave the way for treatments for other conditions, such as stroke, spinal cord injury and sepsis. », concludes Professor Bartlett.

Source : Clinical Drug
Investigations