Patient case: 54-year-old male with Gastric cancer. Genetic variant: PIK3CA (E545K). Other conditions: Depression.

Clinical trial: The Role of the Coagulation Pathway at the Synapse in Prion Diseases

Summary: The study hypothesis is that that the deleterious effect of prions on the brain may be mediated (at least partially) by activation of serine proteases involved in the coagulation system. If this is true, then measurement of the activity of the coagulation system may be a marker of disease onset (in at higher risk individuals such as E200K* carriers) and for disease progression or activity in affected individuals. In addition, modulation of the coagulation system activity may be a potential tool for therapeutic intervention.
  *E200K- E200K mutation (Glu to Lys substitution) in the prion protein gene

Detailed description: We plan to collect Cerebrospinal fluid (CSF) samples for thrombin activity assay in order to test whether there is a difference in thrombin activity in the CSF between CJD (Creutzfeldt-Jakob disease) and non-CJD patients. CSF samples will be obtained from two sources 1. Patients with familial or sporadic CJD and control patients with other neurodegenerative disorders (e.g. SDAT**, NPH) that will be evaluated in Sheba Medical Center 2. From our collaborating group of Prof. Zerr in the German Prion Referral Center at the University of Gottingen which has a collection of thousands of CSF samples from patients with familial and sporadic CJD as well as ideal controls with other degenerative brain disease.
  The study has 2 sections:
  1. Prospective part in which we plan to recruit 25 patients with CJD and 25 patients with other types of dementia from Sheba Medical Center (SMC). Prior to inclusion in the study a senior neurologist will interview the patient and will verify that he fully understands the objectives of the study and he is mentally qualified to sign the informed consent form (severely demented patients who will not be able to adequately consider the participation in the study will be excluded).
  Cognitive performance will be evaluated using the Mini-mental Status Examination and Frontal Assessment Battery scales.
  No clinical data other than the cognitive assessment and those needed for the clinical work up will be especially collected for this study.
  2. Retrospective part in which CSF samples from CJD patients and patients with other type of dementia will be shipped to us from our collaborators in Germany ans will be assayed for Thrombin activity. We plan to recruit to this part of the study 100-200 CJD patient CSF samples and a same number of samples from age matched controls.
  Thrombin activity (for samples from both parts of the study) will be assayed as follows: CSF sample will be placed in a black 96 well dish (10 per well). Thrombin activity will be measured by a fluorometric assay, quantifying the cleavage of the synthetic peptide substrate Boc-Asp(OBzl)-Pro-Arg-AMC*** (I-1560, Bachem, Switzerland, 13 molar final concentration). Measurements will be performed by the Infinite 2000 microplate reader (Tecan, infinite 200, Switzerland) with excitation and emission filters of 360±35 and 460±35 nm, respectively. CSF testing for thrombin activity will be conducted in Professor Chapman's laboratory in Sheba. This laboratory is actively engaged in research on the role of thrombin and PAR-1 in diseases of the nervous system and is fully equipped to perform the biochemical and protein levels experiments.
  The assay has the potential for commercialization as a diagnostic test for CJD. In addition, there is the potential to develop therapeutic agents targeting excessive thrombin activation.
  **SDAT=Senile Dementia of Alzheimer Type
  ***AMC= Amino Methyl Coumarin

Eligibility: Inclusion Criteria:
  -  Patient undergoing lumbar puncture test as part of the investigation of cognitive decline.
  Exclusion Criteria:
  -  Patients on anticoagulation or those who have contraindication for undergoing lumbar puncture.

Relevance to patient case: not relevant