VMT Diagnostic of Parkinson Disease

1. VMTDiagnostic of Parkinson Disease You do not have to be a famous boxer or a successful movie star to be concerned about Parkinson

2. Highlights • Medical device - Diagnostic, simple PC based + internet analysis. • Addressing the dire need for effective PD screening test. • Early diagnosis leads to drug treatment that may delay the deterioration of life quality. • Competitive advantage over current manual solutions. • Strong value proposition for patients, neurologists and payers (deferring costly care). • Large target market- many billions in direct and indirect cost. • US Patent 5,772,611, approved in 1998. • FDA clearance 510(k) - “evaluation of visuo-motor performance disturbances”. • Working Prototype • Extensive data base with hundreds of test results • Time to Market – Less then a year. 2

3. Background • VMT (Visuo-Motor-test) method was developed by Prof. Hocherman, of the faculty of medicine at the Technion. • Prof. Hocherman has been involved in basic brain research for over 25 years. • VMT was developed within the framework of his research on neurological motor control. • The technology and the IP rights are owned by a group of four individuals, Prof. Hocherman included. 3

4. Parkinson Disease • Parkinson’s disease is the second most common progressive neurodegenerative disorder, after Alzheimer’s disease. • ~1.5 million Americans are currently diagnosed with PD and 60,000 new cases are diagnosed each year. • More than 2% of the population aged over 65 years are affected. • 5%-10% of patients with PD are misdiagnosed (have Parkinson's but are told they have something else), 4

5. Cost of PD - direct and indirect • The financial cost of Parkinson’s Disease to individuals, government and society combined is in the order of $24 billion per year. • The study finds that indirect costs - e.g. disability payments by government and insurance plans and lost income due to forced early retirement are $15,000 per patient per year. • The direct costs of medicines, surgery, doctor visits, hospitals and nursing homes are $8,800 per patient per year. 5

6. Parkinson Neurological Degenerative Disease • The dopaminergic neurons in the Substantia Nigra are gradually depleted and the levels of Dopamine secretion are diminishing. • The lack of Dopamine hormones has a devastating effect on motor, cognitive functions & emotional state. 6

7. VMTProduct - Overview • The enclosure holds the digitizer at elbow’s level and supports the computer monitor, bringing it to eye level. • It is designed to allow free hand movement across the digitizer’s plane, while hiding the subject's hand from view.

8. The product - operation • TRACING: • A path is displayed on screen. • The subject moves the cursor along the entire path, as accurately as possible. • TRACKING: • A target circle moves along the path, at a predeterminedspeed. • The subject has to maintain the cursor within the moving target. 8

9. The product - operation

10. Data Analysis - complex parameters • The algorithm analyzes and scores the performance in independent tests, comparing Left & Right arms: • Test Time. • (*)Directional Error (DirEr). • (*)Mean percent time of DirEr>50%. • Distance from Path. • Velocity of hand movement. • (*)Number of tracking interruptions. • While some of these parameters are standard, the marked (*) measures are unidue to the present system and are protected by patent. 3/08 10

11. Differential diagnosis of PD • The VMT was tested on various groups: • Early vs. advance PD patients • PD Vs. Essential Tremor patients • PD Vs. Normal subjects 11

12. Current methods for diagnosis of PD UPDRS is the standard manual scale based on performance and cognitive tasks. It takes 20-30 min of the neurologist time to complete the test. SPECT Imaging Dopamine uptake ligand beta-CIT, a SPECT agent is the most sensitive of biomarkers for the diagnosis of Parkinson's disease. Beta-CIT targets the dopamine transporter on the dopamine neuronal terminals and quantifies the loss of those terminals.

13. Clinical Applications • Parkinson • Screening for early phase PD patients. • Differential diagnosis of PD Vs. Essential Tremor and potentially other cognitive & motor dysfunctions. • Optimization of drug treatment for PD patients. • Non-Parkinson • Evaluation of attention disorders (ADD/ADHD). 13

14. Neuroprotection in Parkinson’s Disease • Written by Prof. Shraga Hocherman, : If a “holy grail” exists in the context of Parkinson’s disease (PD) there is no doubt that it would be a treatment that can slow, stop or even reverse the degeneration of neurons whose death causes the disease • Drugs that treat PD symptoms are available, which offer small to modest degree of neuroprotection. • New approaches that offer great promise are currently being tested, based on cell biology and genetic engineering. 14

15. Drug Treatment - Disease Modification Care giver or Nursing home Early diagnosis of PD Drug treatment delays symptoms Months/years of active life 15

16. Conclusions from Hocherman’s Publicationsbased on more then 400 patients • VMT test requires high-level motor planning and cognitive capabilities that are not assessed by the standard diagnostic test - the UPDRS. • VisuoMotor coordination of hand movements requires complex cognitive skills, controlling movement direction and velocity. A failure of these high-level motor control systems may occur early in the disease and may even precede the occurrence of motor symptoms. • The performance in visuo motor coordination test (VMT) is impaired in early PD patients, either pharmacologically treated or untreated. • VMT system maydifferentiate between Essential Tremor patients who may later develop PD and those who wouldn’t. • Impaired VMT is a pertinent indication for further SPECT imaging in patients with ET, in order to establish a diagnosis of incipient PD. • VMT appears to be a promising, inexpensive and friendly adjunct to the diagnosis of PD. 16

17. Interviews with 3 experts on PD • Prof. M Youdim - Technion Pharmacology: “Drugs for slowing the deterioration of PD are expected soon (Rasagiline), early detection and treatment are critical”. • Prof. H. Bergman - Neurological Physiology, Hadassah: “out of all possible indication, early detection is most important”. • Dr. Sharon, Neurologist , Shiba Medical center, Movement Disorders “for PD patients, no single diagnostic modality can replace all other tests, but for monitoring the effects of medicated PD patients, VMT may serve as a objective quantitative tool”. 17

18. Competitive landscape (preliminary) • No commercial products for the diagnosis or screening of PD. • Existing methods : • UPDRS - is the standard manual scale based on performance and cognitive tasks. • SPECT & pet CT - both imaging modalities are suggested for evaluating the # of lost neurons. • Olfactory - research level claiming that the lost of smelling capability is indicative to PD. 18

19. Advantages • VMT is a breakthrough computer based diagnostic procedure encompasses a highly desirable diagnostic tool in the movement disorders clinic. There is not a similar system in the market and the comparison is made vs. the traditional diagnostic methods which are time consuming, less accurate and do not provide quantified results: • Sensitive and objective system that minimizes false first and second degree errors. • Reliable differential diagnosis between PD and its main alternative condition (essential tremor). • Provides quantitative estimation of the patient's condition. • Cost and time savings - Can be operated by a nurse/technician. • Desk top and inexpensive. • Easy to install and use.

20. ADHD - Attention DisorderHow VMT Technology can be used for such an application Shraga Hocherman, Emanuel Tirosh, Sharon Dobrovski Technion, Faculty of Medicine

21. ADHD Future DevelopmentBackground 1 • Inattention is one of the basic components of ADHD pathology. • ADHD diagnosis relies on daily parents\teachers observations of the child’s behavior, and on a clinical interview, but does not include specific testing of attentional functionality. • Behavioral impairments that lead to a diagnosis of ADHD derive in many cases from deficits that are not related to attention.

22. Basic-Test description • Basic Test: Move a “mouse” controlled cursor so that it remains within a 1cm target circle that moves along a sinusoidal path from one end of the screen to the other. • Loss of the target causes the later to stop in place until re-entered by the cursor. • Performance Criteria:Number of target-losing events (Tracking interruptions).Cumulative time of tracking interruptions.Distance from target center.Lateral deviation from the target’s path.Instantaneous directional error. • Measurements resolution: 1 millisecond; 0.05 millimeter.

23. Testing with distraction • Performance under distraction: Target distracters & Cursor distracters. • The number and combination of distracters determines the attentional demand of the subject. • Assessment of the cost imposed by the attentional load by computing the performance difference between the distracted and the basic task. • Low distraction level: 1 target distracter + 1 cursor distracter. • High distraction level: 3 target distracters + 3 cursor distracters.