–Does anyone think there is room for a lowish-priced antidepressant with a new MOA (not TRD)? I guess ALKS does. I gotta look at the data again but I really didn’t think that drug worked. I guess it’s true what they say, run 4 depression Phase IIIs to get two positive ones. Even JNJ’s data was underwhelming. GP/internist drugs are so scary now after so many flops, but look at Eliquis, doing amazingly well. So is 90s pharma over or not?
–On Acadia I wouldn’t be as worried about the safety as I would be on the commercial opportunities and intellectual property. Also a lot of the gain on this short has been realized.
–Sarepta and Madrigal are the two biotech stocks up the most this year. Congratulations to whoever owns those stocks. One fascinating thing is the success of some medtech stocks, including Align and Abiomed, which were favorites of mine (but mostly my old partner) in 2009-2011!
–Will be glancing at some stocks soon, including Alnylam, Fibrocell, Jazz, Endo and others. Was a bit focused on other matters.
Papers I’ve Read
Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Benoit, et al. Nature Medicine 2017.
An approach to suppress the evolution of resistance in BRAFV600E-mutant cancer. Xue, et al. Nature Medicine 2017.
Seemed like an obvious conclusion to me.
Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis. Nature Medicine 2017.
Well, this is explains why volasertib failed. Isn’t tox supposed to ferret this kind of thing out?
moscaism. Different genotypes present within a cell pool.
myc tag. Another small peptide tag used for protein identification and purification. Similar to the FLAG tags I used in my first experiments.
GFP. green fluorescent protein. A good reporter of gene/protein expression.
SNP (elementary concept, essential importance). single nucleotide polymorphism, a variation in a nucleotide at a specific position.
Hardy-Weinberg equilibrium. In genetics, an equation that predicts allele frequency. Often used to quality check sequencing in GWAS.
eQTL. expression quantitative trait loci – analysis of genetic loci that influence level of mRNA/protein expressed
Sanger sequencing. An older type of DNA sequencing relying on chain terminators. Still used in basic experiments, but not in NGS (next-generation sequencing).
cAMP. messenger molecule created from ATP by adenylate cyclase after a GPCR Gs receptor is activated.
MADRS. Montgomery-Asberg Depression Rating Scale. A commonly used scale for measuring major depression. >20 is depressed. Control patients usually have a rating of 0-1.
SSRI. Selective serotonin reuptake inhibitor. Class of drugs approved for depression including Zoloft (sertraline), Celexa (citalopram), Paxil (paroxetine), Lexapro (escitalopram) and others. All SSRIs are now generic.
Protein Kinase A.
phosphodiesterase. Also known as PDE, a class of enzymes that break phosphodiester bonds, including the one present in cAMP.
anoxia. lack of oxygen.
prefrontal cortex. area of the brain responsible for “executive function” including personality, complex behavior, decision making, etc. Mine is clearly highly developed.
cortical. refering to cortex areas of the brain, not the motor or sensory areas, but “higher” processing
subcortical. “below” cortex structures such as the amygdala, hypothalamus, etc.
bulbar dysfunction. neurological finding resulting in abnormal speech and swallowing. the bulbar structure is composed of the cerebellum, medulla and pons, with the medulla being the “bulb”.
bioavailability (elementary concept, critical importance). a PK measurement that compares the dose administered to the patient with the available drug level in the blood. It is a ratio sometimes indicated by the variable name F. The F of any IV administration of a drug is always 100%. Some drugs have very low bioavailability (10-20%) and pose a potential risk if blood levels are variable. Protein binding is an important consideration in contemplating drug availability in conjunction with bioavailability.
gene amplification. in an oncology context, a copy number change, often induced by selective/evolutionary pressure
splice variants. the product of alternative splicing (very important concept).
prometaphase. the phase in mitosis before metaphase where kinetochores form.
metaphase. the phase in mitosis before anaphase where chromosomes align prior to separation
cytokinesis. when the cytoplasm of a single cell divides into two.
monopolar spindles. a spindle defect.
kinetochore. a protein that forms the attachment point for the spindle to separate sister chromatids.
chromatid. the copy of a chromosome attached to its template by a centromere.
apraxia. the inability to complete a fine motor task.
GPCR. G-protein coupled receptor. 7-transmembrane family of receptors coupled to a G-protein. Very common pharmacological targets.
I hate correcting the media. Some Vanity Fair reporter Emma Stefansky apparently said that my Wu-Tang album was no longer ‘mine’. That’s interesting since I pay for it to be stored and insured every month. Maybe someone can reach out to her and ask her who has it? Because I don’t know, I think I do. Maybe I’m wrong? Let me know.
The same thing applies to my finances. People know about 10% of the story. I’m wealther than I ever have been. Liquidity has always been a struggle for me. I don’t think I’ve ever been really liquid, basically ever. That’s just how it works with serial entrepreneurs who put everything they have into their companies. Elon Musk once said he couldn’t pay his rent. I think mere mortals don’t understand the concept of giving all you’ve got.
I’m sitting pretty though, as the IRS owes me a $4 million refund, I’m hopeful that the insane $7 million judgment gets reversed on appeal (which I’ve already paid most of), and I have about $22 million in uncashed options from my first company that I should probably cash in. It’s been difficult to do basic things like that since I was remanded for “hairjokegate” 2017. I guess I gotta find a notary here, they supposedly have one in the prison, but I’ve only been here for two months. Anyway, my private holdings are growing more valuable by the day, so I find it funny reading all the misinformed stuff about me.
One person told me “eh, don’t correct aynone, it will be even funnier when you buy a sports team and people will say ‘what a comeback'”. But, there’s nothing to “come back” from. Jail is adult time out. I haven’t learned anything profound from this experience, other than doing what most prisoners do, which is to stew and grow more resentful of our overreaching and corrupt law enforcement. I’m innocent and was narrowly convicted with the assistance of witness coercion, the government obtaining illegal evidence and all kinds of other government tricks. They certainly prosecute the person, not the crime. Lucky Luciano, Al Capone, you name it. A bad guy is a bad guy, doesn’t matter what they did. They’re trying to do it to our President as we speak. What law did he violate, so that we can get vengence for the political policies we don’t like? Shame on the FBI–it should be shut down. [End Count of Monte Crisco rant.]
Is Drake’s new album any good?
I’d like to see more responses in comments!!!!