The growing enthusiasm which surrounds the ‘ Huntington world’ is becoming more and more tangible nowadays; not only for the increasing number of participants in international symposiums but also for the great variety which compose them: biologists, chemists, doctors, psychologists, physiotherapists, nutritionists, speech therapists, patients, family members and associations. Everybody does want* to contribute and improve on knowledge, assistance and -above all- progress in research. We came back from the Netherlands keen on working harder to our projects and ideas. Progress on Research Many clinical trials have just ended or are close to ending: some of them with great immediate results, others needing further evidences. Past results are pushing us to improve future strategies and on the 3rd of December 2016 LIRH annual meeting (Rome, at Istituto ‘Leonarda Vaccari’) we will have the chance to face these features with family members and patients. Scientific world is not only relating to an internal laboratory view but paying more attention to patients and clinic. On this occasion, industrial and academic leading figures presented the most awaited clinical trials results.
PRIDE-HD. (pridopidine) It was the most eagerly awaited study . Michael Hayden ( Teva’s Research& Development President) presented the very promising results of this study at the end of the day. We will deeply discuss this subject in a follow-up article at the end of the present one.
FIRST-HD study, led in the USA, showed that Tetrabenazine may be taken in a chemically modified way which is better tolerated by patiens and named Deutetrabenazine (SD-809, made by Auspex Pharma). Deutetrabenazine seems to reduce the intensity of the chorea symptoms (involuntary movements). The impression patients had on their health condition’s improvement was confirmed the clinics’ scientific evidence. A green-lighted answer from Regulatory Authorities is awaited. They will probably need other confirms on the long term use of this drug.
This study was led in France on a hundred of patients , tested the effectiveness of cysteaminebitartrate (RP 103, made by pharmaceutical company Raptor) and was co-funded by the French Health Department in order to verify benefits on motor functions. The study hasn’t still given clear results and needs a longer test phase on a higher number of patients (at least 300/400)
The Action-HD study was led in Germany. Patients were given Bupropion molecule in order to test whether it had an effect on apathy symptom which, as you know, highly compromises both autonomy and everyday life through an influence on cognitive aspects as well as the emotional sphere or the relationship with family members. Unfortunately, they didn’t reach significant results. As concerns this element of the illness, it still remains hard to find a proper approach both for the identification of the correct drug and the assessment tools actually in use. Further research efforts are needed in order to limit the drop out attitude of patients, which is very common in the HD last phases
Expert-HD study is the first clinic study led by the Cardiff University that involved patients from United Kindom, the Netheralds, Germany and Norway, whose aim is to monitor the effectiveness of motor rehabilitation. The study represents an innovative experiment in the clinical research: it is about different rehabilitating exercises with different intensity taken for 50 minutes, three times a week for twelve weeks. Even if only a slight improvement of motor functions was observed, some important conclusion came up: a) rehabilitating is useful and potentially effective B) rehabilitating is helpful while you are taking the treatment but loses power in a long term period. C) it is possible to lead a rehabilitating clinical trial with a standard clinical monitor involving a certain number of centers. Future aims for these kind of researches are represented by extending the study of –at least -6 months while combining a specific and adequate nutritional program.
ONGOING CLINICAL TRIALS:
(Translation coming soon!)
Silenziamento Genico (Anti-Sense-Oligonucleotide - ASO), finanziato da IONIS-ROCHE: primo tentativo, di fase 1 e pertanto molto inziale, di ‘spegnere’ il gene malato e la conseguente produzione della proteina tossica (huntingtina); Il prossimo 3 dicembre a Roma il Prof. Blair Leavitt, che coordina lo studio in Canada, lo illustrerà nel dettaglio. Rappresenta un approccio pioneristico nei pazienti. Il Prof. Blair Leavitt è profondo conoscitore della metodica, vicino alla LIRH e srà, quella del 3 Dicembre, un’occasione unica per discutere con lui personalmente cosa è lecito attendersi nel futuro di questa sperimentazione.
Amaryllis: è uno studio condotto in Canada, finanziato da Pfizer, finalizzato a verificare se l’inibitore PDE10 aiuti i neuroni a comunicare più efficacemente tra loro, in modo da migliorare la coordinazione dei movimenti; i risultati sono attesi per il primo quadrimestre del 2017.
Legato-HD: sta sperimentando un farmaco immunomodulatore già in uso per la sclerosi multipla (laquinimod) ed è condotto anche in Italia. Mantenetevi collegati al nostro sito per avere dettagli sulla fase di reclutamento dello studio che è stata sospesa e dovrebbe riprendere presto.
Signal: sta sperimentando VX15 - prodotto da Vaccinex – che ha da poco ottenuto la designazione di ‘farmaco orfano’ dalla FDA e che sta mostrando un’azione interessante sul processo infiammatorio (come ci si aspetta dal Laquinimod) nel sistema nervoso centrale dei pazienti con malattia di Huntington con il conseguente declino delle facoltà mentali e motorie)
Stair: studio sostenuto dall’azienda farmaceutica AZEVAN, la molecola si chiama SRX246 e potrebbe agire sul sintomo IRRITABILITA’. Si prevede di coinvolgere circa 150 pazienti negli Stati Uniti.
Da ultimo, desideriamo citare uno studio tuttora in corso solo in Francia che, per la prima volta, mette a confronto tre farmaci molto noti ai pazienti: Olanzapina (Zyprexa), Tetrabenazina (Xenazina) e Tiapride (Sereprile), coordinato dalla Prof. Anne-Catherine Bachoud-Levy. I risultati non sono ancora disponibili, ma le impressioni vanno nella direzione attesa, che conferma il concetto che un ‘blocco farmacologico’ dei movimenti involontari non rappresenta sempre ed in tutti i casi un vantaggio.
Il numero di industrie farmaceutiche che si dichiarano interessate ad investire nella ricerca sulla malattia di Huntington è aumentato e nei prossimi 2 anni ci aspettiamo nuovi studi clinici di fase III.
In conclusione: molto si sta muovendo, nuove molecole si stanno sperimentando; di altre, già note, si sta cercando di comprendere meglio i benefici, altre ancora passeranno dalla sperimentazione sull’animale a quella sull’uomo nei prossimi due anni. Vi aspettiamo al nostro convegno il 3 Dicembre a Roma, presso l’Istituto Leonarda Vaccari in Viale Angelico, per raccontarvi ulteriori dettagli e discuterli insieme a voi. La ricerca corre, la speranza ha il diritto di crescere.
AN UPDATE ON THE PRIDE-HD STUDY by Ferdinando Squitieri, MD; PhD
The phase 2 Pride-HD study recently came to the end and the preliminary results were disclosed by Teva Pharma.
The primary endpoint of the Pride-HD study was to evaluate tolerability and efficacy of the molecule ‘pridipodine’ on motor symptoms at certain dosages. The study did not meet its primary endpoint but showed unespected effects on the disease progression.
As a principal investigator and as the Italian study coordinator (Italy was the first Country entering in the Study in Europe), I can say that, according to my experience, this was one of the most challenging clinical trial I have never been involved in.
Pridopidine: this molecule was born thanks to a nobel prize (Dr Carlsson) intuition on the effects of dopamine on the synapsis connections among neurons. Justo Garcia de Yebenes, a well known neurologist from the Università Ramòn y Cajal in Madrid (member of LIRH scientific committee), convinced a small Danish pharma industry (Neurosearch) to test it in a Huntington Disease population. The first clinical trial involved 437 HD patients in Europe (MarmeiHD fase 3 study) and 228 HD patients in US (HART fase 2 study) showing positive results on motor symptoms. Italy was not included at first, but we succeding in being finally included. In the meantime, Teva, a Israeli based multinational, bought pridopidine patent and launched the PRIDE-HD phase 2 study.
PRIDE-HD: The study was planned to last 6 months but it was decided to extend the duration to 1 year, due to new, interesting, unespected information about Sigma-1 receptor effects on neurons connections emerging during the study. Preliminary data show that, after 1 year, pridopidine reduces severity progression at 67,5 and 90 mg twice per day (these dosages are much higher that the ones studied in the previous trials) What’s Next? Although these data are encouraging, that is not enough. What we should expect is a phase 3 study involving more patients, assuming effective dosages. Patients who participated in the Pride-HD study are currently assuming 90 mg pridopidine per day.
Teva Pharma official Press Release: