Current therapies for neurodegenerative diseases such as Parkinson’s, amyotrophic lateral sclerosis, Huntington’s or Alzheimer’s are primarily aimed at combating symptoms and do not address the causes of these symptoms.
A Paradigm Shift in Neurology
With Talineuren, InnoMedica has developed an extraordinary nanocarrier compound. Talineuren enables transportation of a neuroregenerative active substance across the blood-brain barrier in high concentration, where the active substance can unfold a positive, protective effect on affected neurons. Talineuren uses the active agent ganglioside GM1. GM1 occurs naturally in human nerve cells and as active agent promotes the regeneration of these nerve cells. By enabling a regenerative mechanism, Talineuren is suitable for the application in a wide range of neurodegenerative diseases. Talineuren furthermore enables a form of administration suitable for long-term treatment in chronic diseases. InnoMedica will conduct first clinical trials with Talineuren in the indications Parkinson’s disease and ALS. At the same time, additional preclinical research on other possible applications will be conducted.
Brain scan without Talineuren®-treatment
Brain scan with Talineuren®-treatment
MALDI imaging mass spectrometry of brain cross sections of untreated (left) and orally administered Talineuren® treated mice (right). The intensity scale shows the amount of GM1 detected in the brain. Significantly more GM1 is detectable after treatment with Talineuren®.
First Application in Parkinson‘s
In order to improve the current treatment options for Parkinson’s patients, an active substance is needed that can target the causes of the disease and supports endogenous dopamine production restricted by Parkinson’s disease. Dopamine is a substance that occurs in many brain regions and is necessary for the conscious control of movements. A dopamine deficiency can be attributed to the death of dopamine producing nerve cells in the midbrain. Currently existing drugs only treat the symptoms of the disease. Currently, still no treatment exists that addresses the causes of Parkinson’s, that prevents the death of dopamine producing cells, or that regenerates affected nerve cells. Furthermore, with the current treatment of symptoms instead of causes, nerve cells continue to die off during treatment, necessitating constant dosage increases of the active substance. In addition, side effects that further restrict the everyday life of affected patients are frequent with current treatments.
Numerous studies have demonstrated a neuroprotective effect of GM1 as well as its successful application in Parkinson’s disease. For example, Prof. Jay Schneider of Thomas Jefferson University (TJU) was able to demonstrate in a human study with 94 Parkinson’s patients that the progression of the disease is delayed or stopped completely by administration of GM1. When GM1 was administered in addition to continued treatment with other drugs, a long-term improvement in motor function and thus an alleviation of neurological symptoms in Parkinson’s was observed. This improvement could be attributed to the regenerative function of GM1. However, in order to accumulate sufficient amounts of GM1 in the brain for a therapeutic effect, the active agent had to be administered subcutaneously twice a day in this study. The depot effect produced in this way caused painful local skin reactions, which in most cases were unbearable for the patients despite the strong improvements in the disease’s symptoms.
However, in liposomally packaged administration of GM1, the nanocarrier enables a depot effect. Talineuren therefore no longer has to be injected subcutaneously, but can be administered intravenously or even orally. InnoMedica protected this application with a patent already in December 2017 while conducting further research on the drug. In view of the extensive available preclinical data, InnoMedica has submitted an application for a first clinical study with Parkinson’s patients in cooperation with leading neurologists. As soon as Swissmedic's approval allows, first patients will be treated with Talineuren as part of a clinical trial in the second half of 2021.
Orphan Drug Status Thanks to Application in Amyotrophic Lateral Sclerosis (ALS)
In addition to Parkinson’s disease, the efficacy of Talineuren was also tested in preclinical studies in amyotrophic lateral sclerosis (ALS) in cooperation with the University of Bern. In patients with ALS, the motor neurons degenerate very quickly, while mental and sensory functions remain unimpaired. Life expectancy after a diagnosis with ALS is only three to five years. Current therapies delay the progression of the disease and prolong life by a few months. To date, no therapy exists that can demonstrably promote the regeneration of motor neurons. Talineuren promises to strengthen neuromuscular connections, halt the degeneration of motor neurons, and promote the reinnervation of skeletal muscles.
The study results demonstrate good effects in animal models against this currently incurable and virtually untreatable disease. Mice treated with Talineuren showed striking improvements in motor function compared to sick, untreated mice. InnoMedica therefore immediately applied to the EMA and the FDA for orphan drug status, which was granted by both authorities in spring 2021. This status is reserved for drugs intended for the treatment of rare diseases where no effective therapeutic treatments yet exist and grants market exclusivity for multiple years. Such a categorisation also simplifies cooperation with the authorities thereby considerably facilitating progress to market approval. Hence, the study submission for this indication is also planned already in 2021.
Interview with Prof. Dr. Smita Saxena, Research Leader, University of Bern and Inselspital
Treatment Option for Severe Covid-19 Disease Courses
The latest research indicates SARS-CoV-2 as a neuronal disease that enters the nervous system via the respiratory tract. 80% of Covid-19 patients develop neurological symptoms during the course of the disease, which in severe cases lead to prolonged hospitalisation and increased mortality. Talineuren comprehensively protects and regenerates the nervous system and may therefore be of substantial aid in the treatment of corona patients. Talineuren is ready for use in a clinical trial and a timely application in patients with severe courses is possible. Furthermore, Talineuren has successfully been produced in clinical quality multiple times at InnoMedica’s nanofactory in Marly. The expansion of the second modular clean room ensures future production of Talineuren in Switzerland.
The study protocols for the clinical use of Talineuren in the first Parkinson’s patients have been finalised and submitted in 2021. Parts of the dossier can subsequently also be used for the submission of study applications for other indications of Talineuren.
A safety study shall demonstrate the tolerability of Talineuren and render initial evidence on its efficacy in Parkinson’s disease. The risk of toxicity is estimated to be very low, as Talineuren is based on endogenous substances. The study design for the first clinical trial involves 12 patients with Parkinson’s disease, which will be treated with Talineuren at four different dose levels. The study will not include healthy subjects, but only Parkinson’s patients receiving intravenous administrations of Talineuren in addition to their normal treatment. This study design enables collection of data on efficacy in first patients already in the safety study. Clinical trials with free GM1 demonstrated comparatively rapid effects after treatment. Accordingly, initial findings are expected as early as two to three weeks after the first administration in studies with Talineuren. For later phases of the clinical trials with Parkinson’s patients, the inclusion of a control group and the administration of a placebo is being considered. For the recruitment of patients, InnoMedica is working together with the leading neurologist Michael Schüpbach, MD, who is already supporting InnoMedica in the study planning for Talineuren.
As orphan drug status has been granted for Talineuren in ALS, InnoMedica will also prepare a study application for this indication as soon as possible with submission planned in early 2022. Yet another clinical trial with Talineuren will investigate the treatment of Covid-19-related nerve damage. However, because hospitals are operating at capacity due to Covid-19, studies on Covid-19 have been temporarily stopped. Nonetheless, InnoMedica is reviewing a temporary authorisation for the use of medicinal products with Swissmedic for Talineuren therapy of Covid-19-related nerve damage.
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