Signature of the SAVE-BRAIN and SURVI MSD-Avenir projects

On the 18th April 2017, D Blazy (Président du Conseil Scientifique de MSD-Avenir) on the behalf of C Schiever (Président du CA de MSD-Avenir), M Hirsch (Directeur Général de l’AP-HP), the Prof Y Levy (Président Directeur Général de l’INSERM), in the presence of the Prof P Ruszniewski (Doyen de l’UFR de médecine de l’Université Denis Diderot) and of F Crémieux (Directeur du groupe hospitalier Hôpitaux universitaires Paris Nord Val-de-Seine), have signed the partnerships for two ambitious projects entitled SAVE-BRAIN and SURVI in both of which the LVTS is critically implicated.

  • The SAVE-BRAIN program, led by Teams 1, 3 and 5 of the LVTS and the Bichat-Claude Bernard AP-HP Hospital, focuses on reducing brain damage following a stroke by improving the reperfusion process.
  • The SURVI program, led by the teams of the Beaujon Hospital AP-HP  with the participation of Team 1 of LVTS Inserm seeks to improve the prognosis and management of intestinal infarction, or mesenteric infarction.

We are very pleased to support the teams of SAVE BRAIN and SURVI, whose breadth and ambition of the programs contribute to the influence of French research in the world. These research programs are mostly carriers of great hope for patients, through the reduction of numerous sequelae left by a vascular accident. This is the purpose of the mission set by MSDAVENIR two years ago: to take part in the dynamism of public-private research in France in order to better understand, prevent and treat major pathologies” said Cyril Schiever, President of the Board of Directors of MSD-Avenir.

For several years, INSERM has been committed to active public-private partnerships to support health research. This is one of the priorities of the institution’s 2020 Strategic Plan. I congratulate the scientific teams who, just one year after the signing of a framework agreement with MSD-Avenir, have already initiated ambitious research projects carried out directly in the interest of patients affected by stroke” said Pr. Yves Lévy, President and CEO of Inserm.

SAVE BRAIN: To limit the harmful effects of post-stroke reperfusion on cerebral tissues

Of the 150,000 victims of stroke in France each year, the second leading cause of death in the world [1], 80% is related to cerebral ischemic attacks (AIC): one of the arteries that irrigates the brain is clogged and that prevents oxygenated blood from reaching the brain.

Although essential for restoring blood circulation to the brain, reperfusion of the ischemic area following a stroke is often accompanied by toxic mechanisms that damage the brain tissue. This deterioration, due to a high presence of leukocytes in the reperfused blood, can be the cause of severe haemorrhages. Preventing and better controlling the deleterious action of leukocytes is an important route of research. This is the goal of the SAVE-BRAIN program, led by Inserm and AP-HP teams, supported by MSD-Avenir. Their unique work in the world focuses on preclinical studies and seeks to:
1. Develop therapeutic agents targeting CD31 signaling to control leukocyte activation during reperfusion.

2. To limit the tissue damage inflicted by the multimolecular complexes delivered by the leucocytes by directly inhibiting their molecular effectors thanks to active compounds to be delivered during the reperfusion.

Stroke is treated urgently with approaches to alleviate vascular obstructions. However, this leads to an inflammatory response that can in turn inflict damage to the brain. With the help of MSD-Avenir, the SAVE-BRAIN program carried out by several teams of our Inserm U1148 research unit and the Prof Pierre Amarenco‘s Department of Neurology at the BICHAT Hospital will test approaches to limit this damage using molecules/drugs that we have developed and patented with the help of Inserm-Transfert. MSD-Avenir will accompany us to enable us to transform our molecules into usable drugs in humans with the objective of reducing the mortality and severity of sequelae after a stroke” said Prof Antonino Nicoletti, the scientific leader of SAVE-BRAIN.

SURVI: To develop multi-modal and multidisciplinary care to save patients suffering from an intestinal infarction

Despite recent advances in research (digestive surgery, cardiology, resuscitation, etc.), no treatment has succeeded in stemming the mortality of intestinal infarction or acute mesenteric ischemia, which can exceed 80%. The sequelae are burdensome for the survivors. These include extensive bowel resection, the main cause of the short bowel disease, which prevents any possibility of nutritional autonomy.

In February 2016, the first Structure of Intestinal Vascular Emergency (SURVI), dedicated to the management of digestive infarcts and intestinal vascular diseases, opened at the Beaujon AP-HP hospital. This facility offers patients multi-modal and multidisciplinary care (gastroenterology, interventional radiology, vascular and digestive surgery, anesthesia-resuscitation) taking into account the different aspects of the pathology. The first results observed in a pilot study show that the survival rate exceeds 80%.
The SURVI program consists of three components: (i) development of care and capacity, (ii) teaching and (iii) research in association with Team 1 of Inserm 1148. With the support of MSD-Avenir, the teams have the ambition to continue their research in order to:
· To develop early biological markers specific for intestinal ischemia in order to improve its diagnosis;

· Assess diagnostic methods, particularly endoscopic, to confirm the ischemic nature of the intestinal mucosa as soon as the patient is cared for;

· Introduce therapeutic tools to improve emergency diagnosis and ensure better transmission of knowledge (mobile applications, creation of a national registry, medico-economic study, etc.)

The main objective in the management of intestinal infarction has long been focused solely on the survival of the patient, often leading to a major intestinal sacrifice and still associated with high mortality. The paradigm shift was to preferentially target the survival of the intestine, which allowed us to reduce the use of mutilating interventions and ultimately greatly improve the survival of the patients. Hence, the whole strategy is based on: establishing an early diagnosis, considering ischemia as reversible, revascularizing the intestine like the heart or the brain, limiting the use of surgery, preserving life and eating ability. All these aspects, targeted by SURVI, ultimately depend on the viability of the intestine which must be preserved at all costs ” said Prof Olivier Corcos, head of SURVI – Intestinal vascular emergencies at the Beaujon Hospital AP-HP.